The investigations are aimed at the elucidation of the biochemical processes underlying heamostasis in man and thus, in a wider perspective, at the understanding of the pathophysiological mechanisms involved in thrombosis and bleeding manifestations. Three areas of research are of high priority: 1. Structure-function relationships in the fibrinogen molecule. Attempts are being made to localize at the molecular level the structures which are involved in fibrinogen polymerization as a result of release of fibinopeptide A and B. This is done by studying the affinity between fragments of fibrinogen or fibrin and immobilized derivatives of fibrinogen or fibrin. Identification of residues which are critical for function, will be facilitated by chemical modification of amino acid residues by photooxidation, iodination or acylation. 2. Platelet function. In the first phase of these studies the interaction between platelets and fibrinogen in the presence and absence of ADP were investigated. Inhibition analyses will aid in the identification of the structures in fibrinogen involved in the interaction with platelets. The interaction of thrombin with platelets and the ensuing release reaction will be investigated. The thrombin susceptible protein in the platelet membrane will be isolated and characterized. 3. Degradation by fibrinogen and fibrin formation in vivo. The metabolic fate of fibrinogen will be studied by determination of fragments of the molecule in blood. Of particular interest is the COOH-terminal part of the alpha A-chain. The structure of fibrin as formed in blood will be investigated by analysis of fibrin related fragments isolated from clots formed in whole blood from normal individuals with thrombotic diseases. Structural analysis of fibrin in thrombi will also be performed.